Aberrant production of IL-17 cytokines, primarily by T helper-17 (Th17) cells, has been implicated in the development of many inflammatory and autoimmune diseases, such as Psoriasis, Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA). These and other similarly debilitating diseases associated with these cytokines afflict millions of Americans and, in addition, cause highly significant economic burdens. IL-17 (IL-17A) and the functionally and structurally closely related IL-17F are the signature cytokines of Th17 cells; they are members of the larger IL-17 cytokine family, which also includes IL-17C and IL-17E (IL-25), among others. IL-25 has been associated with Th2-type responses and, when dysregulated, may contribute to the development of Asthma. IL-17A and F are not only produced by Th17 cells, but also by a several innate T cells and by innate lymphocytes type 3 (ILC3s), while IL-25 appears to be produced primarily by epithelial cells. IL-17A and F are particularly important in defense of extracellular bacteria and fungi. All IL-17 family cytokines signal via an adaptor protein named CIKS, previously cloned in our laboratory. In the past we have reported on the functional importance of CIKS in collagen-induced arthritis (CIA), a mouse model of RA, and in SLE. CIKS was particular important in development of lupus nephritis, the most fatal form of SLE disease. The latter finding was the first report to clearly implicate a role for IL-17 cytokines in local inflammation in kidneys, i.e. the development of glomerulonephritis. Previously we also identified CIKS as a potential target for therapeutic intervention in psoriasis, a disease that has been closely linked to the actions of the IL-17 cytokine. Mice lacking CIKS were largely protected from the development of imiquimod-induced psoriatic inflammation, a mouse model that closely mimics many aspects of the human disease. We furthermore discovered that IL-17 targeted different cell types to cause the diverse manifestations of the disease. These insights revealed why this cytokine appears to be so central to the development of this disease. In FY 2015 we advanced our understanding of how the cytokine IL-25 contributes to asthma-like allergic lung inflammation. We determined that IL-25 not only targets ILC2 cells to produce IL-13 and IL-5, but it also targets dendritic cells; we showed that IL-25-stimulated dendritic cells were the source of various inflammatory mediators, such as chemokines, which then attracted various inflammatory cells. We furthermore found that CCL17, one of the induced chemokines, rapidly recruited IL-9 producing T cells into the lung. Finally we demonstrated that IL-25 activation of dendritic cells was essential to attract these T cells in the context of house dust mites-induced allergic inflammation, a physiologically relevant model for human asthma.